Retroviral gene transfer is a powerful tool for studying gene expression as well as a model for gene replacement therapy. Previous work by this laboratory has shown that derivatives of the N2 retroviral vector will efficiently transfer genes to murine erythroid cell lines and early hematopoietic progenitor cells. We have modified the N2 vector to contain a human beta globin gene. Recombinant viruses packaged by psi 2 packaging cells were used to infect mouse bone marrow cells. These cells were used to repopulate histocompatible genetically anemic W/Wv mice. Cells were injected directly after infection, or following an additional 48 hours of selection with G4l8, as the N2 beta globin virus also contains a neomycin resistance gene. At various times post infection the peripheral blood of these animals was sampled and analyzed for human beta globin gene expression by immunofluorescent staining. Four weeks post infection the animals repopulated with unselected marrow were 80% repopulated with the infected marrow (as monitored by genetic markers) and 45.5% (5/11) were expressing human beta globin in up to 20% of the peripheral blood cells. The animals repopulated with G4l8 selected marrow were 30% repopulated with the infected marrow and 100% (12/12) were expressing human beta globin in up to 20% of the peripheral blood cells. We are continuing to monitor the expression of human beta globin in these mice.